Cystic Fibrosis

Question 1

If 2 unaffected carriers have a child what are the chances of Cystic fibrosis

Answer 1

1 in 4 as it is an autosomal recessive disease

Question 2

What is the pathophysiology of CF

Answer 2

• It is caused by mutations of the CFTR (cystic fibrosis
transmembrane conductance regulator) gene
• CFTR is a Cl- channel essential in Cl- transport in organs such
as intestines, lungs, sweat glands, kidneys, and pancreas
• Reduced function of chloride channels in epithelium

Increased intracellular NaCl
• Water moves from mucus in airway lumen intracellularly leading to Abnormally viscous secretions

Question 3

Clinical presentation of CF

Answer 3

• Recurrent respiratory tract infections
• Chronic cough
• Salty sweat
• Progressive respiratory failure
• Digital clubbing
• Nasal polyps
• Distal intestinal obstruction
• Meconium ileus (faeces stuck in ileum of newborn)
• Weight loss
• Steatorrhoea (fatty stool due to reduced bile production and impaired pancreatic exocrine function)

Question 4

How to diagnose CF

Answer 4

Carrier testing (CFTR gene sequencing)
• Family history of cystic fibrosis

Prenatal diagnosis (CFTR gene sequencing)
• Chorionic villus sampling or amniocentesis

Newborn screening (NBS) for cystic fibrosis introduced in 2007
• Heel prick test
• IRT (immunoreactive trypsinogen) pancreatic enzyme
If raised:
• Sequence CFTR gene
• Sweat test (gold standard for diagnosing cystic fibrosis)
• NBS made significant difference to prognosis
• Better lung function
• Fewer lung infections
• Better weight gain
• Improved survival

Question 5

Treatments of CF

Answer 5

• Chest physiotherapy to clear the airways of this thick mucus to reduce the chance of airway infection
• Prophylactic (PO) and treatment (PO/IV) antibiotics

Dietician involvement
• Dietary supplements
• Vitamins
• Pancreatic enzymes
• Ursodeoxycholic acid (bile acid reduces cholesterol fraction of biliary lipds - thins bile)

Inhalers/nebulisers
• Mucolytics (DNAse)
• Bronchodilators
• Steroids
• Salt (which is often lost with sweat)
• Annual review – CXR (chest radiograph), USS abdo (abdominal ultrasound exam), bloods

Question 6

What is the moat common CF mutation

Answer 6

ΔF508 - loss of phenylalanine at 508 position of CTFR protein

Question 7

How does the drug lumacaftor aid CF

Answer 7

Reverses folding effect of ΔF508

Question 8

How does ivafactor aid CF

Answer 8

Increases Chloride transport